rs368128605

Positions:

• chr11-1245766-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002458.3(MUC5B):​c.8886T>C​(p.Arg2962=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 1,599,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (0 hom., cov: 28)
  • Exomes 𝑓: 0.026 (0 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -10.6

Genes affected

MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]

MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BP6: Variant 11-1245766-T-C is Benign according to our data. Variant chr11-1245766-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-10.6 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2855/149570) while in subpopulation NFE AF= 0.0245 (1636/66798). AF 95% confidence interval is 0.0235. There are 0 homozygotes in gnomad4. There are 1403 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2855 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC5B	NM_002458.3	c.8886T>C	p.Arg2962=	synonymous_variant	31/49	ENST00000529681.5	NP_002449.2
MUC5B-AS1	NR_157183.1	n.57-3128A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5	c.8886T>C	p.Arg2962=	synonymous_variant	31/49	5	NM_002458.3	ENSP00000436812	P1
MUC5B-AS1	ENST00000532061.2	n.57-3128A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2856 AN: 149452 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00541

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00548

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0151

GnomAD3 exomes AF: 0.0245 AC: 6076 AN: 247944 Hom.: 0 AF XY: 0.0243 AC XY: 3277 AN XY: 134620

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.00481

Gnomad ASJ exome AF: 0.0261

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00861

Gnomad FIN exome AF: 0.0664

Gnomad NFE exome AF: 0.0320

Gnomad OTH exome AF: 0.0264

GnomAD4 exome AF: 0.0258 AC: 37431 AN: 1449650 Hom.: 0 Cov.: 57 AF XY: 0.0254 AC XY: 18329 AN XY: 721422

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.00517

Gnomad4 ASJ exome AF: 0.0249

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00848

Gnomad4 FIN exome AF: 0.0621

Gnomad4 NFE exome AF: 0.0279

Gnomad4 OTH exome AF: 0.0242

GnomAD4 genome AF: 0.0191 AC: 2855 AN: 149570 Hom.: 0 Cov.: 28 AF XY: 0.0192 AC XY: 1403 AN XY: 73000

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.00540

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00569

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0150

Alfa AF: 0.0285 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.7
DANN	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs368128605; hg19: chr11-1266996;